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The N-methyl-D-aspartate (NMDA) receptor complex: a stoichiometric analysis of radioligand binding domains
K H Thedinga1, M S Benedict, G E Fagg
1Pharmaceuticals Research Division, Ciba-Geigy Ltd., Basel, Switzerland.
Abstract:
A stoichiometric analysis of pharmacological domains within the N-methyl-D-aspartate (NMDA) receptor complex was made by evaluating the binding of L-[3H]glutamate, [3H]CPP, [3H]glycine and [3H]MK-801 to purified synaptic membranes isolated from rat telencephalon. The binding of all radioligands exhibited pharmacological and kinetic properties consistent with the labeling of homogeneous populations of sites associated with the NMDA receptor. However, strychnine-insensitive [3H]glycine binding sites were present at close to 2-fold the density of the other sites examined. These data, together with recent electrophysiological and receptor autoradiographic findings, are utilized as a basis for hypotheses regarding the ratio of transmitter recognition, allosteric and channel binding sites within the NMDA receptor complex.